Short macrocyclic peptides in sponge genomes
Short macrocyclic peptides in sponge genomes
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DOI：
10.1073/pnas.2314383121
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发表时间：
2024-03-12
影响因子：
11.1
通讯作者：
Schmidt，Eric W.
中科院分区：
文献类型：
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作者：
Lin，Zhenjian;Agarwal，Vinayak;Schmidt，Eric W.
海绵（多孔动物）含有许多肽类代谢产物，具有强大的生物活性，在塑造海洋生态中发挥着重要作用。共生细菌在核糖体上和非核糖体上产生生物活性的“海绵”肽是公认的。在这里，我们证明了海绵本身也产生许多生物活性大环肽，如phakellistatin和相关的富含脯氨酸的大环肽（PRMP）。使用柱花草海绵转录组，方法被开发来寻找编码46个不同的RiPP型核心肽的序列，其中10个编码先前鉴定的PRMP序列。在此基础上，对波纹轴孢海绵的基因组和转录组进行了分析，发现了35个PRMP前体肽，编码31个独特的核心肽序列。其中至少有11种产生的环肽存在于海绵中，可以通过质谱法进行表征，包括stylissamides A-D和7种以前未描述的化合物。前体肽在A. corrugatagenome，确认其动物来源。这些肽含有信号肽序列和高度重复的识别序列-在单个前体中具有多达25个PRMP拷贝的核心肽元件。与没有PRMP的海绵相比，PRMP海绵难以置信地富含潜在分泌的多肽，在单个转录组中发现了> 23，000个单独的信号肽编码基因。PRMP生物合成基因和神经肽在其生物合成逻辑方面的相似性表明与环状肽相关的基本生物学，可能表明整个动物王国中信号肽翻译后修饰的广泛和未被充分认识的多样性。
Sponges (Porifera) contain many peptide-specialized metabolites with potent biological activities and significant roles in shaping marine ecology. It is well established that symbiotic bacteria produce bioactive “sponge” peptides, both on the ribosome (RiPPs) and nonribosomally. Here, we demonstrate that sponges themselves also produce many bioactive macrocyclic peptides, such as phakellistatins and related proline-rich macrocyclic peptides (PRMPs). Using theStylissa carterisponge transcriptome, methods were developed to find sequences encoding 46 distinct RiPP-type core peptides, of which ten encoded previously identified PRMP sequences. With this basis set, the genome and transcriptome of the spongeAxinella corrugatawas interrogated to find 35 PRMP precursor peptides encoding 31 unique core peptide sequences. At least 11 of these produced cyclic peptides that were present in the sponge and could be characterized by mass spectrometry, including stylissamides A-D and seven previously undescribed compounds. Precursor peptides were encoded in theA. corrugatagenome, confirming their animal origin. The peptides contained signal peptide sequences and highly repetitive recognition sequence-core peptide elements with up to 25 PRMP copies in a single precursor. In comparison to sponges without PRMPs, PRMP sponges are incredibly enriched in potentially secreted polypeptides, with >23,000 individual signal peptide encoding genes found in a single transcriptome. The similarities between PRMP biosynthetic genes and neuropeptides in terms of their biosynthetic logic suggest a fundamental biology linked to circular peptides, possibly indicating a widespread and underappreciated diversity of signaling peptide post-translational modifications across the animal kingdom.